Imidazopyridine Derivatives as Modulators of TNF Activity

A compound of formula (I) or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof, or a glucuronide derivative thereof, or a co-crystal thereof:

• wherein
• E represents a covalent bond;
• or E represents —S(O)2— or —N(R4)—;
• or E represents an optionally substituted straight or branched C1-4 alkylene chain;
• Q represents a covalent bond;
• or Q represents —O—, —S—, —S(O)—, —S(O)2—, —S(O)(NR5)—, —N(R5)—, —C(O)N(R5)—, —N(R5)C(O)—, —S(O)2N(R5)— or —N(R5)S(O)2—;
• or Q represents an optionally substituted straight or branched C1-6 alkylene chain optionally comprising one, two or three heteroatom-containing linkages independently selected from —O—, —S—, —S(O)—, —S(O)2—, —S(O)(NR5)—, —N(R5)—, —C(O)N(R5)—, —N(R5)C(O)—, —S(O)2N(R5)— and —N(R5)S(O)2—;
• Y represents C3-7 cycloalkyl, aryl, C3-7 heterocycloalkyl or heteroaryl, any of which groups may be optionally substituted by one or more substituents;
• Z represents hydrogen, halogen or trifluoromethyl;
• or Z represents C1-6 alkyl, C3-7 cycloalkyl, aryl, C3-7 heterocycloalkyl, C3-7 heterocycloalkenyl or heteroaryl, any of which groups may be optionally substituted by one or more substituents;
• or Z represents —Z1-Z2 or —Z1—C(O)—Z2, either of which moieties may be optionally substituted by one or more substituents;
• Z1 represents a divalent radical derived from an aryl, C3-7 heterocycloalkyl or heteroaryl group;
• Z2 represents aryl, C3-7 heterocycloalkyl, C3-7 heterocycloalkenyl or heteroaryl;
• R1, R2 and R3 independently represent hydrogen, halogen, cyano, nitro, hydroxy, trifluoromethyl, trifluoromethoxy, —ORa, —SRa, —SORa, —SO2Ra, —SF5, —NRbRc, —NRcCORd, —NRcCO2Rd, —NHCONRbRc, —NRcSO2Re, —N(SO2Re)2, —NHSO2NRbRc, —CORd, —CO2Rd, —CONRbRc, —CON(ORa)Rb, —SO2NRbRc or —SO(NRb)Rd;
• or C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C4-7 cycloalkenyl, C3-7 cycloalkyl(C1-6)alkyl, aryl, aryl(C1-6)-alkyl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl(C1-6)alkyl, C3-7 heterocycloalkenyl, C4-9 heterobicycloalkyl, heteroaryl, heteroaryl(C1-6)alkyl, (C3-7)heterocycloalkyl(C1-6)alkyl-aryl-, heteroaryl(C3-7)heterocycloalkyl-, (C3-7)cycloalkyl-heteroaryl-, (C3-7)cycloalkyl-(C1-6)alkyl-heteroaryl-, (C4-7)cycloalkenyl-heteroaryl-, (C4-9)bicycloalkyl-heteroaryl-, (C3-7)heterocycloalkyl-heteroaryl-, (C3-7)heterocycloalkyl(C1-6)alkyl-heteroaryl-, (C3-7)heterocycloalkenyl-heteroaryl-, (C4-9)heterobicycloalkyl-heteroaryl- or (C4-9)spiroheterocycloalkyl-heteroaryl-, any of which groups may be optionally substituted by one or more substituents;
• R4 and R5 independently represent hydrogen or C1-6 alkyl;
• Ra represents C1-6 alkyl, aryl, aryl(C1-6)alkyl, heteroaryl or heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted by one or more substituents;
• Rb and Rc independently represent hydrogen or trifluoromethyl;
• or C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl(C1-6)alkyl, heteroaryl or heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted by one or more substituents;
• or
• Rb and Rc, when taken together with the nitrogen atom to which they are both attached, represent azetidin-1-yl, pyrrolidin-1-yl, oxazolidin-3-yl, isoxazolidin-2-yl, thiazolidin-3-yl, isothiazolidin-2-yl, piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, piperazin-1-yl, homopiperidin-1-yl, homomorpholin-4-yl or homopiperazin-1-yl, any of which groups may be optionally substituted by one or more substituents;
• Rd represents hydrogen;
• or C1-6 alkyl, C3-7 cycloalkyl, aryl, C3-7 heterocycloalkyl or heteroaryl, any of which groups may be optionally substituted by one or more substituents;
• and
• Re represents C1-6 alkyl, aryl or heteroaryl, any of which groups may be optionally substituted by one or more substituents.